Opioids Agonists (Exam II) Flashcards
What are opioids effects on the CO₂ medullary center?
- Opioids inhibit the CO₂ medullary center.
Differentiate opioids from narcotics.
- Opioids = all exogenous substances that bind to endogenous opioid receptors.
- Narcotic = any substance that can produce dependence (stupor)
What two types of opioid chemical structures are there?
- Phenanthrenes
- Benzylisoquinolines
What types of drugs are Phenanthrenes?
What types of drugs are benzylisoquinolines?
- Phenanthrenes: Morphine & codeine
- Benzylisoquinoline: Papaverine
What is papaverine mostly used for?
Treating intra-arterial barbiturate administration (dilates the highly constricted artery).
What portions of the brain are the source of descending inhibitory signals?
- Thalamus
- PAG
- Locus Coeruleus
What endogenous substances have the same effect as opioids?
Endorphins, Enkephalins, and Dynorphines.
Presynaptic inhibition of what neurotransmitters occurs with opioid administration?
- ACh
- Dopamine
- NE
- Substance P
How do opioids modulate pain at the cellular level?
At pre/postsynaptic opioid receptor sites in CNS
- ↑ K⁺ permeability (hyperpolarization)
- inactivate Ca⁺⁺ channel
Where are opioid receptors located in the brain?
- PAG
- Locus Coeruleus
- RVM (rostral ventral medulla)
- Hypothalamus
Where is the primary site of opioid receptors in the spinal cord?
Substantia gelatinosa (aka Laminae 2)
Where is/are opioid receptors found outside the CNS?
- Sensory neurons & immune cells
What are the four (most important) types of opioid receptors?
- Μu1 (μ₁)
- Μu2 (μ₂)
- Κappa (κ)
- Delta (δ)
Which opioid receptor(s) is/are responsible for respiratory depression & physical dependence?
- Μu2 and δ
Which receptors are responsible for constipation?
- Μu2 primarily
- δ (less)
Which receptors can cause urinary retention?
Are there any receptors that cause diuresis when bound?
- Retention: Μu1 and δ
- Diuresis: κ
All opioid receptors induce analgesia at both the brain and the spinal cord. T/F?
- False. Μu2 receptors only cause analgesia at the spinal cord level.
What opioid receptors have low abuse potential when bound?
Μu1 and κ
Which opioid receptor is responsible for euphoria, bradycardia, hypothermia, and miosis when bound?
Mu1
What agonists bind to each of the four opioid receptors?
- Mu1 & Mu2 = endorphins, morphine, synthetics.
- κ = dynorphins.
- δ = enkephalins.
Describe the adverse side effects of opioids on the cardiovascular system.
- ↓BP from ↓SNS tone
- ↓HR or histamine release = ↓BP
What possible cardiovascular benefits do opioids provide?
- Myocardial ischemia protection (decrease oxygen demand)
What are the respiratory effects of opioids?
What would symptoms of overdose be?
- Depressed CNS response to CO₂ causing a right shift of PaCO₂ (↑)
- Overdose = apnea, miosis, coma.
What drug would treat opioid ventilatory depression but not reverse analgesia?
How?
- Physostigmine would by increasing CNS ACh levels.
What would cause a leftward shift in PaO₂?
What would cause a rightward shift?
- Leftward: Metabolic acidosis (to breathe off all that CO₂)
- Rightward: sleep → opiates → anesthesia
Why should caution be used when administering opioids to head trauma patients?
- Opioids ↓CBF and possibly ICP
What musculoskeletal abnormality occurs with opioid administration?
What makes this condition worse?
How is it treated?
- Skeletal chest wall and abdominal muscle rigidity.
- Mechanical ventilation
- Muscle relaxants and/or naloxone
What are sphincter of Oddi spasms?
Which drugs can cause this?
- Biliary smooth muscle spasm
- Fentanyl (99%), Morphine (53%), and Meperidine (61%). (Opioids)
What drugs should be used for ERCP cases?
- Non-opioids (multimodal approach w/ NSAIDs, gabapentin, etc.)
How are opioid-induced sphincter of Oddi spasm’s treated?
- Naloxone
- Glucagon (2mg IV given incrementally) and causes no opioid antagonism.
How long does it take (generally) to develop tolerance to opioids?
What causes tolerance?
- 2-3 weeks
- Downregulation (desensitized and decreased number of opioid receptor)
What is the dosage of morphine?
When does it peak?
How long does it last?
- 1 - 10 mg IV
- Peak: 15 - 30 minutes
- Duration: 4-5 hours
How is morphine metabolized?
What is the active metabolite and its significance?
- Glucuronidation in the liver.
- Morphine-6-glucuronide = comprises only 5-25% of morphine metabolites but is an active anaglesic causing late resp depression.
What would occur with morphine overdose in a renal failure patient?
- Prolonged ventilatory depression.
What receptors does meperidine agonize?
- μ and κ receptors
- α2 receptors as well
What are the analogues of meperidine?
What other drugs does meperidine have a similar organic structure to?
- Fentanyl & it’s derivatives
- Lidocaine & Atropine
How potent is Meperidine? (comp)
How long does it last?
- 10% as potent as morphine
- Duration: 2-4 hours
What is the primary indication for meperidine?
What dose is used?
- Post-operative shivering
- 12.5mg IV
When should meperidine not be used?
- Bronchoscopies (promotes coughing)
How potent is fentanyl?
- 75 - 125 x morphine.
